An Interactive Tool for the Optimization of Freeze-Drying Cycles Based on Quality Criteria

Among existing dehydration methods, freeze-drying has unique benefits for the stabilization and preservation of biological activity of pharmaceutical products but remains an expensive and time-consuming process. A user-friendly software tool was developed, allowing for interactive selection of process operating condition profiles in order to maximize process productivity while insuring product quality preservation. The software is based on a dynamic, one-dimensional heat and mass transfer model, which can accurately represent both the primary and secondary drying stages and the gradual transition between them. The model was validated in a wide range of operating conditions: ? 25 to + 25°C shelf temperature and 10 to 34 Pa total pressure. By comparing a reference sucrose solution with a formulated pharmaceutical product containing polyvinylpyrrolidone (PVP), it is shown that controlling product properties such as glass transition temperature and sorption isotherm can reduce the minimum achievable cycle duration by 12 h (33%).     

Monitoring the bacterial population dynamics during the ripening of Galician chorizo,a traditional dry fermented Spanish sausage

The dynamics of the bacterial population throughout the ripening of Galician chorizo, a traditional dry fermented sausage produced in the north-west of Spain, were investigated by using classical and molecular approaches.     

Improved Thermal Behavior of Multiple Linked Arrays of Silicon Nanowires Integrated into Planar Thermoelectric Microgenerators

Low-dimensional structures have been shown to be promising candidates for enhancing the thermoelectric properties of semiconductors, paving the way for integration of thermoelectric generators into silicon microtechnology. With this aim, dense arrays of well-oriented and size-controlled silicon nanowires (Si NWs) obtained by the chemical vapor deposition (CVD)-vapor–liquid–solid (VLS) mechanism have been implemented into microfabricated structures to develop planar unileg thermoelectric microgenerators (μTEGs). Different low-thermal-mass suspended structures have been designed and microfabricated on silicon-on-insulator (SOI) substrates to operate as microthermoelements using p-type Si NW arrays as the thermoelectric material. To obtain nanowire arrays with effective lengths larger than normally attained by the VLS technique, structures composed of multiple ordered arrays consecutively bridged by transversal microspacers have been fabricated. The successive linkage of multiple Si NW arrays enabled the development of larger temperature differences while preserving good electrical contact. This gives rise to small internal thermoelement resistances, enhancing the performance of the devices as energy harvesters.     

Introducing the fractional-order Darwinian PSO

One of the most well-known bio-inspired algorithms used in optimization problems is the particle swarm optimization (PSO), which basically consists on a machine-learning technique loosely inspired by birds flocking in search of food. More specifically, it consists of a number of particles that collectively move on the search space in search of the global optimum. The Darwinian particle swarm optimization (DPSO) is an evolutionary algorithm that extends the PSO using natural selection, or survival of the fittest, to enhance the ability to escape from local optima. This paper firstly presents a survey on PSO algorithms mainly focusing on the DPSO. Afterward, a method for controlling the convergence rate of the DPSO using fractional calculus (FC) concepts is proposed. The fractional-order optimization algorithm, denoted as FO-DPSO, is tested using several well-known functions, and the relationship between the fractional-order velocity and the convergence of the algorithm is observed. Moreover, experimental results show that the FO-DPSO significantly outperforms the previously presented FO-PSO.     

Neural cell growth on TiO2 anatase nanostructured surfaces

Titanium oxides have anti-inflammatory activity and tunable electrochemical properties that make them attractive materials for biomedical applications. This work investigated the compatibility of nanometric coatings of low-temperature phases of TiO₂ with neurons in 4-day and 10-day cultures, using different cell densities to quantify cell survival and neurite extension. TiO₂ films were prepared by sol–gel and thermal treatment (250–450 °C) of hydrolyzed titanium tetra-isopropoxide on electrically conducting or insulating slides. The conducting substrates were not passivated by the nanometric oxide layer and could be used as electrodes. Characterization of the films showed nano-structured TiO₂ containing exclusively Ti⁺⁴ valence in anatase and amorphous phases. When coated with polylysine, all films permitted good neuron attachment and survival for at least ten days in culture. However, they generally reduced neurite growth compared to cell culture borosilicate glass, with dendrites more affected than axons. The analyses of surface topography, hydrophilicity, charge and chemical composition revealed that TiO₂ chemistry was the main factor responsible for neurite inhibition.     

Resistance to freezing and frozen storage of Streptococcus thermophilus is related to membrane fatty acid composition.

The resistance to freezing and frozen storage of Streptococcus thermophilus was related to the fatty acid composition of the cell membrane. The effects of four experimental factors were investigated on the fatty acid concentrations and on the recovery of acidification activity of S. thermophilus stored at -20 degrees C by using a complete experimental design: incorporating oleic acid in the culture medium, fermentation pH, addition of glycerol as cryoprotective agent and duration of storage. The acidification activity decreased during the freezing and the frozen storage of S. thermophilus. The storage time slightly enhanced the unsaturated fatty acid concentrations. The addition of glycerol did not modify the fatty acid composition but increased the resistance to frozen storage. The addition of oleic acid and the decrease of the fermentation pH enhanced the ratio unsaturated:saturated fatty acids and improved the recovery of the acidification activity. These results indicate that the resistance to frozen storage was closely related to the membrane fatty acid composition. We interpreted this as an adaptation of S. thermophilus to the addition of oleic acid and the unfavorable growth conditions that corresponded to a low fermentation pH.     

Do Drug-likeness Rules Apply to Oral Prodrugs?

This paper describes a comparative analysis of the physicochemical and structural properties of prodrugs and their corresponding drugs with regard to drug-likeness rules. The dataset used in this work was obtained from the DrugBank. Sixty-five pairs of prodrugs/drugs were retrieved and divided into the following categories: carrier-linked to increase hydrophilic character, carrier-linked to increase absorption, and bioprecursors. We compared the physicochemical properties related to drug-likeness between prodrugs and drugs. Our results show that prodrugs do not always follow Lipinski's Rule of 5, especially as we observed 15 prodrugs with more than 10 hydrogen bond acceptors and 18 with a molecular weight greater than 500 Da. This fact highlights the importance of extending Lipinski's rules to encompass other parameters as both strategies (filtering of drug-like chemical libraries and prodrug design) aim to improve the bioavailability of compounds. Therefore, critical reasoning is fundamental to determine whether a structure has drug-like properties or could be considered a potential orally active compound in the drug-design pipeline.     

Recombinant IGF-1 Induces Sex-Specific Changes in Bone Composition and Remodeling in Adult Mice with Pappa2 Deficiency

Deficiency of pregnancy-associated plasma protein-A2 (PAPP-A2), an IGF-1 availability regulator, causes postnatal growth failure and dysregulation of bone size and density. The present study aimed to determine the effects of recombinant murine IGF-1 (rmIGF-1) on bone composition and remodeling in constitutive Pappa2 knock-out (ko/ko) mice. To address this challenge, X-ray diffraction (XRD), attenuated total reflection-fourier transform infra-red (ATR-FTIR) spectroscopy and gene expression analysis of members of the IGF-1 system and bone resorption/formation were performed. Pappa2^ko/ko mice (both sexes) had reduced body and bone length. Male Pappa2^ko/ko mice had specific alterations in bone composition (mineral-to-matrix ratio, carbonate substitution and mineral crystallinity), but not in bone remodeling. In contrast, decreases in collagen maturity and increases in Igfbp3, osteopontin (resorption) and osteocalcin (formation) characterized the bone of Pappa2^ko/ko females. A single rmIGF-1 administration (0.3 mg/kg) induced short-term changes in bone composition in Pappa2^ko/ko mice (both sexes). rmIGF-1 treatment in Pappa2^ko/ko females also increased collagen maturity, and Igfbp3, Igfbp5, Col1a1 and osteopontin expression. In summary, acute IGF-1 treatment modifies bone composition and local IGF-1 response to bone remodeling in mice with Pappa2 deficiency. These effects depend on sex and provide important insights into potential IGF-1 therapy for growth failure and bone loss and repair.